OP0300 INCREASING THE ETANERCEPT DOSE IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS: DOES IT HELP REACHING THE TREATMENT TARGET? A POST-HOC ANALYSIS OF THE BEST4KIDS RANDOMISED CLINICAL TRIAL
Authors: B. Van Dijk, S. A. Bergstra, J. M. Van den Berg, D. Schonenberg-Meinema, L. W. A. Van Suijlekom-Smit, M. Van Rossum, Y. Koopman-Keemink, R. Ten Cate, C. Allaart, D. M. C. Brinkman, P. C. E. Hissink Muller
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Etanercept is a frequently used second-line therapy for juvenile idiopathic arthritis (JIA). It is unknown whether higher doses of etanercept result in better clinical outcomes, but most studies only evaluated doses up to the most commonly used 0.8 mg/kg/week (max 50mg/week).[1] Although higher doses are used off-label in clinical practice, the literature lacks an in-depth description of patients receiving such treatment. <h3>Objectives</h3> To describe the clinical course of JIA-patients that received high-dose etanercept (1.6 mg/kg/week; max 50mg/week) as part of the Best4Kids trial. <h3>Methods</h3> In a single-blinded treatment-strategy trial, patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treatment-strategy arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX+6 weeks prednisolone and (3) combination therapy MTX+etanercept.[2] A protocolised treat-to-target approach aiming for inactive disease was used during 24 months follow-up. Treatment was escalated in case of persistent disease-activity or tapered in case of inactive disease. In any treatment-arm patients could eventually escalate from regular to high-dose etanercept alongside MTX 10mg/m2/week. For comparison we studied patients who did not receive high-dose etanercept due to decisions overriding the trial-protocol by the treating paediatrician and/or the patient/parents. <h3>Results</h3> Of the 94 randomised patients, 32 received high-dose etanercept (69% female, median age 6 years (IQR 4-10), median time from baseline 10 months (7-16), median dose 1.3 mg/kg/week (1.1-1.5)). Follow-up was up to 2 years from baseline (median follow-up 24.6 months). Clinical measures of disease-activity decreased largely within 3 months (Figure 1): median VAS-physician from 12 to 4 (p=0.022), VAS-patient/parent from 38.5 to 13 (p=0.003), VAS pain from 35.5 to 15 (p=0.030), number of active joints from 2 to 0.5 (p=0.12) and JADAS10 from 7.2 to 2.8 (p=0.008). Functional status (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern of clinical parameters over time was observed in 11 patients (73% girls, median age 8 (IQR 6-9)) who were not escalated to high-dose etanercept despite eligibility according to trial-protocol. In both the high-dose and the comparison group the percentage of patients with inactive disease 6 months after eligibility for dose-increase was 56%. In the high-dose group, 18 out of 32 patients (56%) experienced 26 infectious adverse events (AEs, on average 0.20 events per visit following dose-increase). No serious AEs (SAEs) were recorded after dose-increase. Among the 11 patients who did not receive high-dose etanercept, 4 patients (36%) subsequently experienced 5 infectious AEs (on average 0.11 events per visit); this included one SAE requiring hospitalisation. Findings were similar when one patient who switched to infliximab, instead of maintaining the regular etanercept dose, was excluded from the comparison group. <h3>Conclusion</h3> Escalation to high-dose etanercept was generally followed by meaningful clinical improvement within 3 months. However, non-escalators experienced comparable improvement. These data do not suggest superior clinical outcomes after etanercept dose increase, while there was a potential trend for more (non-severe) infectious AEs. Larger studies are needed to more closely examine outcomes, adverse events and cost-effectiveness of high dose etanercept. <h3>References</h3> [1]Verstegen RHJ et al. Arthritis Care Res (Hoboken). 2022. doi: 10.1002/acr.24859 [2]Hissink Muller P et al. Ann Rheum Dis. 2019;78(1):51-9. doi: 10.1136/annrheumdis-2018-213902. <h3>Acknowledgements</h3> N/A. <h3>Disclosure of Interests</h3> None Declared.